Breast Pathology: Differential Diagnostic Dilemmas
Dr. Christopher Elston
Case 8 -
Dr. Puay Hoon Tan
A 72 year old Chinese lady presented in 2002 with recurrent palpable lumps in the right breast.
Imaging studies revealed multiple subareolar nodular densities with well-defined borders, without stromal
distortion or suspicious microcalcifications. The largest nodule measured 1.9 cm in diameter. After a
fine needle aspiration procedure, the lumps were surgically excised. The submitted section is from the
Further clinical history disclosed that a right breast lesion first appeared in 1995, when a 2 cm
firm nodular lump in the upper outer quadrant was discovered on breast self-examination. There were no
skin changes, nipple retraction or discharge. This lump was excised then but recurred twice in 1998 and
1999 before this current presentation.
She had previously undergone total hysterectomy for squamous cell carcinoma of the uterine cervix,
and was afflicted with hypertension and diabetes mellitus, which were controlled with medical treatment.
The resected surgical specimen comprised breast tissue measuring 8 cm in largest dimension with
overlying skin and nipple. There were four separate nodules measuring from 0.5 cm to 2.0 cm.
Macroscopically, they appeared lobulated, pale yellow white and firm in consistency.
Case 8 - Slide 1
Sections of all four nodules revealed lobulated aggregates of bilayered cells forming round tubules,
separated by basement membrane-like material. Glandular structures or solid groups of cells were
bordered circumferentially by cells with clear cytoplasm in keeping with myoepithelial cells. Epithelial
cells contained scanty eosinophilic cytoplasm; nuclei were round and regular with even chromatin and
prominent nucleoli. Myoepithelial cells possessed clear cytoplasm. Rare mitoses were observed. There
was no cellular pleomorphism or tumour necrosis. Microcalcifications were not seen. The nodules
appeared relatively well circumscribed, without obvious infiltration into adjacent fibrotic breast
parenchyma. However, tissue around the lesions demonstrated peripheral duct papillomas and usual type
The nipple was unremarkable. Surgical margins were clear of lesional tissue.
Immunohistochemistry showed cytokeratin ( Cam 5.2) reactivity for the epithelial cells, with smooth
muscle actin (SMA) decorating the myoepithelial cells.
Features were of adenomyoepithelioma (AM).
Review of the previous pathology material disclosed that the diagnosis of AM for this patient was
first established in 1995 on an excision biopsy, and the current excised lesion showed histological
similarities. Focal dilated ducts with papillomatous areas were present in the original 1995 excision.
At that time, the reporting pathologist had raised the caveat that the lesion, though not malignant,
- Adenosis tumour/Nodular adenosis
- Intraductal papilloma
- Nipple adenoma
- Tubular adenoma
The patient remained on follow-up, without evidence of further breast disease at last review in
Adenomyoepithelioma (AM) of the breast is an uncommon tumour, many of which may represent variants of
intraductal papilloma. Hamperl first described this entity in 1970. Most reports since have been single
case studies although some involved larger numbers of patients. There are three variants described for
this tumour: spindle-cell, tubular, and lobulated, and histological features are generally distinctive
enough for an accurate diagnosis to be made.
Histologic differential diagnoses for this case include the adenosis tumour/nodular adenosis, which
does not refer to a true neoplastic lesion, but is a term used when adenosis or sclerosing adenosis
produces a palpable lump. Its microscopic appearances are essentially those of an increase in ductular
units or acini resulting in an expanded nodular mass. The presence of sclerosing adenosis will
additionally disclose compressed ductular spaces and conspicuous myoepithelial cells. A
pseudoinfiltrative pattern may be discerned. The key difference from an AM lies in the relative
prominence of myoepithelial cells, which while noticeable in sclerosing adenosis, does not assume that
balanced biphasic appearance of AM with fairly equal proportions of luminal epithelial and myoepithelial
Similarly, an intraductal papilloma may be mistaken for an AM, especially since AM can be associated
with an intraductal growth pattern. In this current case, the majority of the lesion was composed of
closely apposed bilayered tubules without much participation by a papillary component with fibrovascular
cores. It was noted however, that there were intraductal papillomas in the surrounding breast tissue.
The prominence of myoepithelial cells also indicated a lesion with a myoepithelial element.
Nipple adenoma, also referred to as florid papillomatosis of the nipple, may be a differential
diagnostic consideration as it manifests as a subareolar or nipple lump, like the clinical presentation
in this case. In contrast from AM which is often lobulated and circumscribed, nipple adenoma or florid
papillomatosis tends to have more ill-defined boundaries, accompanying marked usual epithelial
hyperplasia, and incorporate a focal papillary pattern. Bloody nipple discharge is the most frequent
Tubular adenoma is regarded as a variant of pericanalicular fibroadenoma, whereby the tubules are
closely packed, with scant intervening stroma, and a florid adenosis-like appearance. Small amounts of
luminal secretion may be present, and the lesion may in part disclose more conventional fibroadenoma
areas. Unlike AM, the myoepithelial component does not assume the same degree of prominence.
Other histologic differential diagnoses include ductal adenoma, pleomorphic adenoma, and adenoid
cystic carcinoma. Ductal adenoma is closely related to intraductal papilloma, with the main histologic
difference being the absence of well developed fronds and fibrovascular cores. Pleomorphic adenoma is
nosologically associated with AM, but demonstrates chondroid or chondromyxoid foci. Adenoid cystic
carcinoma is also another lesion related to AM, with characteristic appearances of cribriform structures
and cylindromatous material. The distinction between AM and adenoid cystic carcinoma becomes more
challenging when collagenous spherulosis supervenes in AM.
It has been recommended that the term AM is applied to only lesions that do not fall into more
traditional categories such as papilloma or adenosis, and which display significant participation by
myoepithelial cells. This is because AM is regarded by some authors as being associated with borderline
or malignant behaviour, possibly leading to its being unnecessarily treated aggressively.
AMs are in general benign tumours that are amenable to local excision. Their characteristic biphasic
appearances can be corroborated by immunohistochemical studies, with cytokeratins highlighting the
luminal epithelial cell population, while S100, p63, calponin, smooth muscle actin and other
myoepithelial markers will decorate the myoepithelial cells. S100 however, is known to be reactive for
both luminal epithelial and myoepithelial cells, and may not be a good discriminant between these 2 cell
Local recurrences are usually due to incomplete resection, mostly from multinodularity and peripheral
duct extension, akin to our case. A malignant neoplasm can originate in an AM, and this can be in the
form of epithelial, myoepithelial or biphenotypic malignant alterations. Histologically, there are
increased mitotic activity, necrosis, cellular pleomorphism and peripheral infiltrative growth.
Tavassoli has reported the tubular variant of AM, ill-defined boundaries with lesional tubules
extending into and blending with adjacent normal ducts, multiple satellite lesions leading to incomplete
excision, and concurrent carcinoma arising within the lesion, as features predictive of local recurrence.
In summary, this case represents an AM that has recurred several times, likely a consequence of
incomplete excision. There are no histologic features to suggest malignancy, and the clinical follow-up
after this last wider resection with negative margins has seen no further recurrent disease.
Final Diagnosis: Adenomyoepithelioma.
- Hamperl H. The myoepithelia (myoepithelial cells): normal state; regressive changes; hyperplasia; tumours. Curr Top Pathol 1970; 53: 161–213.
- Tavassoli FA. Myoepithelial lesions of the breast. Myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma. Am J Surg Pathol 1991; 15: 554–568.
- Rosen PP. Adenomyoepithelioma of the breast. Hum Pathol 1987; 18: 1232–1237.
- McLaren BK, Smith J, Schuyler PA et al. Adenomyoepithelioma. Clinical, histologic, and immunohistologic evaluation of a series of related lesions. Am J Surg Pathol 2005; 29: 1294-1299.
- Loose JH, Patchefsky AS, Hollander IJ et al. Adenomyoeithelioma of the breast. A spectrum of biologic behaviour. Am J Surg Pathol 1992; 16: 868–876.